The relationship between monoamine uptake and a variety of diseases and conditions continues to be investigated in an effort to find compounds with both improved efficacy and selectivity so as to eliminate unwanted side effects. One such monoamine, serotonin (5-hydroxytryptamine), has been studied extensively because of its known association with a variety of mammalian disorders. A number of compounds have been shown to have an effect on serotonin. For example, the hydrochloride salt of fluoxetine (dl-N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propanamine) is a selective serotonin uptake inhibitor presently undergoing clinical evaluation for the treatment of depression, eating disorders, alcoholism, and other disorders. Similarly, tomoxetine hydrochloride ((-)-N-methyl-3-phenyl-3-(2-methylphenoxy)propanamine hydrochloride) is a selective inhibitor of norepinephrine uptake being investigated clinically for its antidepressant activity. These compounds are among many taught in U.S. Pat. Nos. 4,018,895, 4,194,009, and 4,314,081 as being potent blockers of the uptake of various physiologically active monoamines including serotonin, norepinephrine and dopamine.
U.S. Pat. No. 4,207,343 discloses 1-phenyl-3-(substituted phenoxy)propanamines again having the ability to block a variety of monoamines.